Automated test equipment (ATE) relates to any testing assembly that performs a test on a device or material under test. ATE assemblies may be used to execute automated tests that quickly perform measurements and generate test results that can then be analyzed. An ATE assembly may be anything from a computer system coupled to a meter, to a complicated automated test assembly that may include a custom, dedicated computer control system and many different test instruments that are capable of automatically testing electronics parts and/or performing measurements. ATE systems both reduce the amount of time spent on testing devices to ensure that the device or material functions as designed and serve as a diagnostic tool to determine the existence of any problems or complications before the device or material reaches the consumer.
For example, ATE can be used in the pharmaceutical industry to ensure that the dry granulation process was a success. Dry granulation is a pharmaceutical formulation process that produces mixed products without adding liquids. Forming granules without moisture requires compacting the powders. Dry granulation is a process in which the particles of a uniform powder mixture are forced to adhere to one another under pressure and then the resultant compact is milled into large particles that have desirable flow characteristics. When the powder blend is compacted by applying force to the powder, it results in considerable size enlargement. The resulting compact is referred to as a ribbon.
The bonding of materials together in the granules reduces the tendency of the components to segregate during processing, which in turn results in content uniformity in the final dosage form.
The two conventional ways of obtaining the compact using dry granulation is slugging or roller compaction. Slugging typically involves using tablet presses for the compaction process. Large tablets are produced in a heavy duty tableting press. However, because it is inefficient, it is rarely used. For example, the powders may not possess enough natural flow to feed the product uniformly, resulting in various degrees of density in the final product.
The preferred method for performing compaction for pharmaceuticals is roller compaction. Roller compaction comprises squeezing the powder between two rollers to produce a sheet of materials or a ribbon. At a given force, depending on the amount of powder conveyed to the rollers, the powder is compacted to a predefined ribbon thickness.
FIG. 1 illustrates an example of a conventional roller compactor (or chilsonator). A roller compactor typically comprises three major parts: a) a powder feeder comprising an inlet funnel with agitator 120, an inlet funnel 124, a feed auger 121 and a tamp auger 122; b) a compaction unit in which powder is compacted between two counter rotating press rollers 125 to a ribbon; and c) a size reduction unit comprising a rotor 126 in which the ribbon is milled to the desired particle size. The roller compactor uses an auger-feed system that will consistently deliver powder uniformly between the press rollers 125. The ribbon is then milled into granules in order to make a flowing powder that can be fed into the tablet press. Accordingly, the powders are compacted into a ribbon between the rollers 125 and milled through a low-shear mill.
Conventionally, there are two types of roller compactors, a fixed gap roller compactor and a variable gap roller compactor. Both consist of the three major parts described above, but differ in the way in which the smallest distance or gap between the rolls is realized. In a fixed gap roller compactor, the compaction force varies with the amount of powder that enters the rollers. By contrast, in the variable gap roller compactor the distance between the rollers changes with the amount of powder drawn into the compaction area to yield a constant force. The fixed gap roller compactor results in a ribbon with constant thickness and variable density while the variable gap roller compactor results in a ribbon with constant density and variable thickness.
Changes in ribbon density typically cause large fluctuations in granulate properties. In ribbon formulation, efforts are made to determine the uniformity and density of the ribbon because the ribbon mixture represents the component makeup of the pharmaceutical. Traditionally, the density of ribbons is measured using microindentation hardness testing. Microindentation hardness testing typically involves making a constant pressure dent in a designated location on different areas of the ribbon. Subsequently, the depth of the dent is measured using microscopy. This is a manual measurement that requires physically cutting the ribbon, denting the ribbon with the indentation device, and finally measuring the indentation with a microscope.
Microindentation hardness testing is not ideal because it is slow and invasive and, therefore, not suited for on-line testing. Because microindentation hardness testing is not an on-line method, the time period between the test and analysis to verify the density of the ribbon is long. This can lead to significant delays and a large amount of wasted product if the problem is detected too far into the process.
Micro X-ray computed tomography is a well-known spatially localized imaging technique that is used to measure the local density of a ribbon. However, similar to microindentation hardness testing, micro X-ray tomography is not well-suited to real-time online applications.